Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C14H21N3O |
| Molecular Weight | 247.336 |
| Optical Activity | ( + ) |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@@H](N)[C@H]1CC[C@@H](CC1)C(=O)NC2=CC=NC=C2
InChI
InChIKey=IYOZTVGMEWJPKR-IJLUTSLNSA-N
InChI=1S/C14H21N3O/c1-10(15)11-2-4-12(5-3-11)14(18)17-13-6-8-16-9-7-13/h6-12H,2-5,15H2,1H3,(H,16,17,18)/t10-,11-,12-/m1/s1
| Molecular Formula | C14H21N3O |
| Molecular Weight | 247.336 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
Y-27632, originally synthesized by Mitsubishi Tanabe Pharma Corporation, is a selective and a strong ROCK inhibitor, which activates the ROCK signal cascade. It was found, that the inhibition of ROCK was beneficial for the prevention of systemic lupus erythematosus, which possibly by suppressing NF-κB activation. Y-27632 can promote both the ex vivo and in vitro proliferation of limbal epithelial cell proliferation. The in vivo enhanced epithelial wound healing further implies that the Y-27632 may act as a new strategy for treating limbal stem cell deficiency. Preliminary human cases confirmed that ROCK inhibitor eye drops were considered effective for treatment of corneal edema associated with cataract surgery.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) |
0.22 µM [Ki] | ||
Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) |
0.3 µM [Ki] | ||
Target ID: Q13464 Gene ID: 6093.0 Gene Symbol: ROCK1 Target Organism: Homo sapiens (Human) |
0.22 µM [IC50] | ||
Target ID: O75116 Gene ID: 9475.0 Gene Symbol: ROCK2 Target Organism: Homo sapiens (Human) |
0.3 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Preventing | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
PubMed
| Title | Date | PubMed |
|---|---|---|
| The role of Rho-kinases in IL-1β release through phagocytosis of fibrous particles in human monocytes. | 2015-01 |
|
| ROCK-dependent ATP5D modulation contributes to the protection of notoginsenoside NR1 against ischemia-reperfusion-induced myocardial injury. | 2014-12-15 |
|
| Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy. | 2013-04-30 |
|
| A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. | 2013-04-15 |
|
| RhoGEF17, a Rho-specific guanine nucleotide exchange factor activated by phosphorylation via cyclic GMP-dependent kinase Iα. | 2013-03 |
|
| Critical roles of Rho-associated kinase in membrane blebbing and mitochondrial pathway of apoptosis caused by 1-butanol. | 2012-09 |
|
| GEF-H1/RhoA signalling pathway mediates lipopolysaccharide-induced intercellular adhesion molecular-1 expression in endothelial cells via activation of p38 and NF-κB. | 2012-03 |
|
| Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. | 2011-10-30 |
|
| Capsaicinoids regulate airway anion transporters through Rho kinase- and cyclic AMP-dependent mechanisms. | 2011-10 |
|
| Reactive oxygen species-dependent RhoA activation mediates collagen synthesis in hyperoxic lung fibrosis. | 2011-06-01 |
|
| Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway. | 2011-05 |
|
| Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure. | 2011-01-01 |
|
| Regulation of retinoschisin secretion in Weri-Rb1 cells by the F-actin and microtubule cytoskeleton. | 2011 |
|
| Oxidative stress and alterations in actin cytoskeleton trigger glutathione efflux in Saccharomyces cerevisiae. | 2010-12 |
|
| Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells. | 2010-11 |
|
| Luteinizing hormone receptor-stimulated progesterone production by preovulatory granulosa cells requires protein kinase A-dependent activation/dephosphorylation of the actin dynamizing protein cofilin. | 2010-09 |
|
| Phosphatase of regenerating liver-1 promotes cell migration and invasion and regulates filamentous actin dynamics. | 2010-08 |
|
| The protective effect of Rho-associated kinase inhibitor on aluminum-induced neurotoxicity in rat cortical neurons. | 2010-07 |
|
| Substituted 2H-isoquinolin-1-one as potent Rho-Kinase inhibitors. Part 1: Hit-to-lead account. | 2010-06-01 |
|
| Up-regulation of the RhoA/Rho-kinase signaling pathway in corpus cavernosum from endothelial nitric-oxide synthase (NOS), but not neuronal NOS, null mice. | 2010-04 |
|
| Protective effects of Y-27632 on acute dichlorvos poisoning in rats. | 2010-03 |
|
| Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin. | 2010-03 |
|
| The suppressive effect of Rho kinase inhibitor, Y-27632, on oncogenic Ras/RhoA induced invasion/migration of human bladder cancer TSGH cells. | 2010-01-05 |
|
| Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells. | 2009-12 |
|
| Agonist-biased signaling via proteinase activated receptor-2: differential activation of calcium and mitogen-activated protein kinase pathways. | 2009-10 |
|
| Suppression of hepatitis C virus replication by protein kinase C-related kinase 2 inhibitors that block phosphorylation of viral RNA polymerase. | 2009-10 |
|
| Statin's excitoprotection is mediated by sAPP and the subsequent attenuation of calpain-induced truncation events, likely via rho-ROCK signaling. | 2009-09-09 |
|
| Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. | 2009-09 |
|
| Dual pathway activated by tert-butyl hydroperoxide in human airway anion secretion. | 2008-11 |
|
| Effects of a selective Rho-kinase inhibitor Y-27632 on oxidative stress parameters in acute dichlorvos poisoning in rats. | 2008-10 |
|
| Calcium sensitization in human esophageal muscle: role for RhoA kinase in maintenance of lower esophageal sphincter tone. | 2008-10 |
|
| Simvastatin inhibits central sympathetic outflow in heart failure by a nitric-oxide synthase mechanism. | 2008-07 |
|
| Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a Rho kinase/p38 kinase pathway. | 2008-05-01 |
|
| Nitric oxide does not downregulate Rho-kinase (ROCK-2) expression in rat coronary endothelial cells. | 2008-02 |
|
| Beneficial effects of the Rho kinase inhibitor Y27632 in murine puromycin aminonucleoside nephrosis. | 2008 |
|
| Simvastatin enhances induction of inducible nitric oxide synthase in 3T3-L1 adipocytes. | 2007-09 |
|
| Simvastatin inhibits TNFalpha-induced invasion of human cardiac myofibroblasts via both MMP-9-dependent and -independent mechanisms. | 2007-08 |
|
| Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis. | 2007-04 |
|
| Dermal condensation formation in the chick embryo: requirement for integrin engagement and subsequent stabilization by a possible notch/integrin interaction. | 2007-03 |
|
| Organized migration of epithelial cells requires control of adhesion and protrusion through Rho kinase effectors. | 2007-03 |
|
| Azithromycin has a direct relaxant effect on precontracted airway smooth muscle. | 2006-12-28 |
|
| Roles of stretch-activated cation channel and Rho-kinase in the spontaneous contraction of airway smooth muscle. | 2006-12-15 |
|
| Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway hyperresponsiveness after the early and late asthmatic reaction. | 2006-09-26 |
|
| Intracellular signal transduction for migration and actin remodeling in vascular smooth muscle cells after sphingosylphosphorylcholine stimulation. | 2006-09 |
|
| Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy. | 2006-08 |
|
| Rho-kinase inhibitor, Y-27632, has an antinociceptive effect in mice. | 2006-07-10 |
|
| Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells. | 2006-07-01 |
|
| An MLCK-dependent window in late G1 controls S phase entry of proliferating rodent hepatocytes via ERK-p70S6K pathway. | 2006-07 |
|
| Defective RhoA/Rho-kinase signaling contributes to vascular hypocontractility and vasodilation in cirrhotic rats. | 2006-03 |
|
| Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. | 1997-10-30 |
Patents
Sample Use Guides
in patients: Y-27632 (10 mM), eye drops topically
in mice: 5mg/kg Y-27632 was intravenously injected
Route of Administration:
Other
Myc-tagged ROCK-I precipitated from lysates of HeLa cells overexpressing this kinase was incubated with 330 μg of protein/ml of histone type 2 and 1 μM ATP at 30°C. Recombinant ROCK-I was then incubated with various concentrations of ATP at 37°C for 30 min, and the enzyme kinetics was analyzed. This analysis revealed the Michaelis-Menten kinetics for this reaction, and the Km value for ATP was calculated to be 0.15 μM by the double reciprocal plot of the reaction. To elucidate the inhibition mechanism of Y-27632, the reaction was further performed in the presence of 0.3 and 1 μM Y-27632. It was shown, that the addition of Y-27632 increased the apparent Km values for ATP of ROCK-I in a concentration-dependent manner without any change in the Vmax value. These findings suggest that Y-27632 inhibited ROCK-I by competing with ATP for its binding to the kinase. Similar results were obtained with ROCK-II, and the Ki values of Y-27632 were estimated to be 0.22 and 0.30 μM for ROCK-I and ROCK-II, respectively. Selectivity of inhibition by Y-compound was then examined by comparing their Ki values for two other Rho effector kinases, citron kinase and PKN, as well as PKCα. The Ki values of the Y-compound for citron kinase and PKN were at least 20 times higher, and the Ki values for PKCα were about 200 times higher than those for ROCK kinases.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 22:02:11 GMT 2025
by
admin
on
Mon Mar 31 22:02:11 GMT 2025
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| Record UNII |
0X370ROP6H
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| Record Status |
Validated (UNII)
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| Record Version |
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-
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0X370ROP6H
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300000057012
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DTXSID7043740
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DB08756
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Y-27632
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146986-50-7
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
Competitive with ATP
COMPETITIVE INHIBITOR
Ki
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TARGET -> INHIBITOR |
